Abstract

Background

Previous studies found an association of greater adherence to placebo medication with
better outcomes. The present study tested whether this association was explained by
any of the following factors: 1) adherence to other medications, 2) healthcare behaviors,
3) disease risk, or 4) predicted degree of adherence. Data included information on
more than 800 risk factors from 27,347 subjects in two randomized controlled trials
of hormone therapy in the Women's Health Initiative.

Results

Greater adherence to placebo was not associated with colon cancer but was substantially
and significantly associated with several diverse outcomes: death, myocardial infarction,
stroke, and breast cancer. Adherence to hormone therapy was only weakly associated
with outcomes. The WHI risk factors only poorly predicted degree of adherence, R2 < 4%. No underlying factors accounted for the association between placebo adherence
and outcome.

Conclusion

The results suggest that adherence to placebo is a marker for important risk factors
that were not measured by WHI. Once identified these risk factors may be used to increase
the validity of observational studies of medical treatment by reducing unmeasured
confounding.